The metabolic significance of copper in mammals, which include humans, has long been recognized. An increased number of human disorders have been associated with copper deficiency similar to disorders observed with copper deficiency in animals. These include anemia, abnormal bone formation, reproductive failure, heart failure, bone abnormalities associated with spontaneous fracture and arterial and cardiac aneurysm.
While it is of paramount importance to maintain adequate copper levels through appropriate dietary intake, it is equally significant to avoid an excessive copper burden that can result in copper poisoning or copper toxicity. The clinical manifestations of copper poisoning in mammals have been known and well described in various publications. These manifestations, which are similar to other metal poisoning, include a metallic taste in the mouth, nausea, vomiting, diarrhea and host of other disorders.
Copper toxicity in mammals may arise due to specific genetic defects, environmental exposure and increased body burden associated with aging. The most notable example of a genetic metabolic defect in human is seen in patients with Wilson's disease. In such patients, copper accumulates in the liver, renal tubules, cornea, brain and other organs causing damage to these structures.
Toxic levels of copper have also been noted in cases of exposure. Accidental ingestion of copper sulfate is not uncommon in children. Some of the more common cases of copper toxicity result from drinking water, foods cooked in copper vessels, soft drinks served from defective equipment and alcoholic beverages brewed or stored in copper lined containers. Industrial exposure to copper, such as exposure to copper oxide fumes, is also common although such exposures result more in dermatologic and respiratory symptoms. Age-related copper toxicity has also been observed due to an accumulation in tissue levels of copper.
Regardless of whether copper toxicity is due to a genetic defect, results from environmental or industrial exposure, or comes about because of aging tissues, its adverse and toxicological symptoms can only be eliminated if the host is capable of systematically disposing of the excess copper.
Heretofore, copper excretion from animals was promoted by treatment with penicillamine, a chelating agent. However, as will hereinafter be discussed, while treatment of animals with penicillamine results in enhanced copper excretion from the system, the administration of this therapeutic agent also results in significant zincuresis as well as losses of other essential trace elements from the system which disturbs the metabolic operation of the body. Loss of zinc is a very serious matter, since this element is involved in more than 125 enzymatic processes in the mammalian body.
In view of these disadvantages of treatment with penicillamine, investigators have directed their attentions to other forms of therapy for diseases resulting from excess copper levels in the system and its attendant physiological toxicity problems. In order to make-up for the zincuresis, some have prescribed oral administration of zinc in dosages designed to alleviate the zincuresis effect of penicillamine therapy. So far as is known, there is no treatment method presently available for reducing the copper level in mammals without concomitant reduction or depletion of zinc from the system.
Accordingly, it is an object of the present invention to provide a method of treatment of mammals whereby their copper burden is reduced without adverse metabolic or other toxic effects.
It is a further object of this invention to provide a method of treatment of mammals to reduce their copper level without any clinically significant zincuresis.
It is still a further object of this invention to administer non-toxic inorganic cobalt compounds, including cobalt salts or cobalt chelates to mammals in order to reduce their copper level to chemically acceptable and non-toxic levels.
It is yet another object of this invention to treat mammals with cobalt chloride or dicobalt ethylenediaminetetraacetic acid (CO.sub.2 EDTA) to reduce their copper level without simultaneously reducing their zinc level or depleting from their systems other desirable trace metals.
The foregoing and other features and advantages of the present invention will become more evident from the ensuing detailed description and the accompanying figures.